Journal article
Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: an NRG Oncology study
Gynecologic oncology, Vol.161(1), pp.113-121
02/02/2021
DOI: 10.1016/j.ygyno.2021.01.025
PMCID: PMC7994192
PMID: 33541735
Abstract
Background: Successfully combining targeted agents with chemotherapy is an important future goal for cancer therapy. However, an improvement in patient outcomes requires an enhanced understanding of the tumor biomarkers that predict for drug sensitivity. NRG Oncology/Gynecologic Oncology Group (GOG) Study GOG-86P was one of the first attempts to combine targeted agents (bevacizumab or temsirolimus) with chemotherapy in patients with advanced endometrial cancer. Herein we performed exploratory analyses to examine the relationship between mutations in TP53, the most commonly mutated gene in cancer, with outcomes on GOG-86P. Methods: TP53 mutational status was determined and correlated with progression-free survival (PFS) and overall survival (OS) on GOG-86P. Results: Mutations in TP53 were associated with improved PFS and OS for patients that received bevacizumab as compared to temsirolimus (PFS: HR 0.48, 95% CI 0.31, 0.75; OS: HR: 0.61, 95% CI 0.38, 0.98). By contrast, there was no statistically significant difference in PFS or OS between arms for cases with WT TP53. Conclusions: This exploratory study suggests that combining chemotherapy with bevacizumab, but not temsirolimus, may enhance PFS and OS for patients whose tumors harbor mutant p53. These data set the stage for larger clinical studies evaluating the potential of TP53 mutational status as a biomarker to guide choice of treatment for endometrial cancer patients. Clintrials.gov: NCT00977574.
Details
- Title: Subtitle
- Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: an NRG Oncology study
- Creators
- Kimberly K. Leslie - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USAVirginia L. Filiaci - Roswell Park Cancer InstituteAdrianne R. Mallen - University of IowaKristina W. Thiel - University of IowaEric J. Devor - University of IowaKatherine Moxley - University of Oklahoma Health Sciences CenterDebra Richardson - University of Oklahoma Health Sciences CenterDavid Mutch - Washington University in St. LouisAngeles Alvarez Secord - Duke University Health SystemKrishnansu S. Tewari - University of California, Irvine Medical CenterMegan E. McDonald - University of IowaCara Mathews - Brown UniversityCasey Cosgrove - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteSummer Dewdney - Rush University Medical CenterYovanni Casablanca - Walter Reed National Military Medical CenterAmanda Jackson - University of CincinnatiPeter G Rose - Case Western Reserve UniversityXunClare ZhouMichael McHale - University of California, San DiegoHeather Lankes - Nationwide Children's HospitalDouglas A. Levine - Gynecologic Oncology GroupCarol Aghajanian - Memorial Sloan Kettering Cancer Center
- Resource Type
- Journal article
- Publication Details
- Gynecologic oncology, Vol.161(1), pp.113-121
- DOI
- 10.1016/j.ygyno.2021.01.025
- PMID
- 33541735
- PMCID
- PMC7994192
- NLM abbreviation
- Gynecol Oncol
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Grant note
- DOI: 10.13039/100009730, name: Stand Up To Cancer; DOI: 10.13039/100000054, name: National Cancer Institute
- Language
- English
- Date published
- 02/02/2021
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984318328502771
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